POLYMORPHISM IN THE TUMOR-NECROSIS-FACTOR-ALPHA PROMOTOR REGION AND IN THE HEAT-SHOCK-PROTEIN-70 GENES ASSOCIATED WITH MALIGNANT-TUMORS

BACKGROUND. Tumor necrosis factors (TNFs) and heat shock protein 70 (h sp70) are determining factors in immunologic mechanisms to tumor cells . The authors designed a case-controlled study to investigate the pote ntial association of the polymorphisms of TNF-alpha and of hsp70-2 and hsp70-hom genes with malignant tumors. METHODS, The authors used an a llele specific polymerase chain reaction to characterize the variation of the TNF-alpha promotor region in 124 unrelated Tunisian patients w ith malignant tumors (non-Hodgkin's lymphoma, breast carcinoma, and ot her tumors) and 106 healthy control subjects. Using polymerase chain r eaction and restriction enzyme digestion, polymorphic analysis of hsp7 0-2 and hsp70-hom genes was performed in patients with non-Hodgkin's l ymphoma, in those with breast carcinoma, and in control subjects. RESU LTS. Analysis of TNF-alpha polymorphism in patients with malignant tum ors and in control subjects demonstrated a high relative frequency of the TNF2 allele in the cancer patients. The relative risk (RR) of lymp homa was especially high in association with TNF1/TNF2 heterozygotes ( RR = 6.7; P less than or equal to 0.0001). Polymorphism analysis of th e hsp70-2 and hsp70-hom genes in patients with lymphoma and in those w ith breast carcinoma revealed that these patients had highly significa nt differences in the genotypic distribution of these biallelic loci c ompared with the control subjects. Homozygosity for one hsp70-2 allele was significantly associated with lymphoma (RR = 18.2; P less than or equal to 0.0001) and with breast carcinoma (RR = 16.3; P less than or equal to 0.001). CONCLUSIONS, Tunisian persons carrying the TNF2 alle le may have an increased risk of cancer. In this study, non-Hodgkin's lymphoma and breast carcinoma were significantly associated with polym orphism in hsp70 genes. (C) 1997 American Cancer Society.